The first complete mitochondrial genome of the hawkmoth Marumba saishiuana (Lepidoptera: Sphingidae) and insights into its phylogenetic position.

In this study, we sequenced and analyzed the complete mitogenome of Marumba saishiuana Okamoto, 1924. The complete mitogenome sequence of M. saishiuana is circular, 15,662 bp in size and encodes 13 protein-coding genes (PCGs), two ribosomal RNA genes (rRNAs), 22 transfer RNA genes (tRNAs), and a control region (CR). Nucleotide composition is highly biased toward A + T nucleotides (81.2%). Most of 13 PCGs initiate with the standard start codon of ATN, except cox1, which starts with CGA. Phylogenetic analyses were performed using nucleotide sequences. A total of 32 Smerinthinae species were selected. The topology based on mitogenome showed that M. saishiuana, M. gaschkewitschii, and M. sperchius formed a clade, and this indicated that M. saishiuana was a member of genus Marumba. Polyptychus trilineatus was the most closely related to genus Marumba on the phylogenetic tree reconstructed by mitogenomes.

Synthesis of 7'-Arylidenespiro[indoline-3,1'-pyrrolizines] and 7'-Arylidenespiro[indene-2,1'-pyrrolizines] via [3 + 2] Cycloaddition and ß-C-H Functionalized Pyrrolidine.

The acetic acid catalyzed three-component reaction of pyrrolidine, aromatic aldehydes, and 3-arylideneoxindolin-2-ones in refluxing toluene afforded functionalized 7'-arylidenespiro[indoline-3,1'-pyrrolizines] in good yields and with high diastereoselectivity. The similar three-component reaction with 2-arylidene-1,3-indanediones also gave 7'-arylidenespiro[indene-2,1'-pyrrolizines] in good yields. However, the reaction with 3-phenacylideneoxindoles resulted in a mixture of spiro[indoline-3,1'-pyrrolizines] and 7'-arylidene-substituted spirooxindoles in moderate yields. The reaction mechanism included generation of azomethine ylides, ß-C-H functionalization of pyrrolidine, and sequential [3 + 2] cycloaddition. The obtained spirooxindole derivatives were investigated by in vitro evaluation against mouse colon cancer cells CT26 and human liver cancer cells HepG2 by MTT assay.

Diastereoselective synthesis of dispirooxindoles via [3+2] cycloaddition of azomethine ylides to 3-phenacylideneoxindoles and evaluation of their cytotoxicity.

The three-component reaction of 1,2,3,4-tetrahydroisoquinoline, isatins and 3-phenacylideneoxindoles in refluxing ethanol afforded dispiro[indoline-3,1'-pyrrolo[2,1-a]isoquinoline-3',3'-indolines] (4a-4x) in good yields via 1,3-dipolar cycloaddition of in situ generated azomethine ylide with the exocyclic double bond of 3-phenacylideneoxindoles. 1H NMR spectra and single crystal structures indicated the reaction has high regioselectivity and diastereoselectivity. Furthermore, their biological activities have been preliminarily demonstrated by in vitro evaluation against mouse breast cancer cells 4T1 and human liver cancer cells HepG2 by MTT assay. The results demonstrated that some of the compounds showed cytotoxicities to cell lines of 4T1 and HepG2, and indicated that novel spirooxindoles may become potential lead compounds for further biological screenings of their medicinal applications.

New uses for old drugs: the tale of artemisinin derivatives in the elimination of schistosomiasis japonica in China.

Artemisinin (qinghaosu), extracted from the Chinese herb Artemisia annua L. in 1972, and its three major derivatives--artemether, artesunate and dihydroartemisinin--were firstly identified as antimalarials and found active against all species of the malaria parasite. Since the early 1980s, artemisinin and its derivatives have been found efficacious against Schistosoma spp., notably larval parasites, and artemisinin derivatives have played a critical role in the prevention and treatment of human schistosomiasis in China. Currently, China is moving towards the progress of schistosomiasis elimination. However, the potential development of praziquantel resistance may pose a great threat to the progress of elimination of schistosomiasis japonica in China. Fortunately, these three major artemisinin derivatives also exhibit actions against adult parasites, and reduced sensitivity to artemether, artesunate and dihydroartemisinin has been detected in praziquantel-resistant S. japonicum. In this review, we describe the application of artemisinin derivatives in the prevention and treatment of schistosomiasis japonica in China, so as to provide tools for the global agenda of schistosomiasis elimination. In addition to antimalarial and antischistosomal actions, they also show activities against other parasites and multiple cancers. Artemisinin derivatives, as old drugs identified firstly as antimalarials, continue to create new stories.

New insight into praziquantel against various developmental stages of schistosomes.

Praziquantel, due to high efficacy, excellent tolerability, few and transient side effects, simple administration, and competitive cost, is virtually the only drug of choice for treatment of human schistosomiasis. Treatment of schistosomiasis has shown great advances with the introduction of the drug into the therapeutic arsenal in areas that are endemic for the parasite. However, the drug presents various efficacies against different developmental stages of schistosomes, appearing an oddity intermitted mode. The present review article reviews the effects and mechanism of action of praziquantel against schistosomes briefly and suggests the research on this oddity phenomenon.

Effect of praziquantel prolonged administration on granuloma formation around Schistosoma japonicum eggs in lung of sensitized mice.

Schistosomiasis remains a major public health problem and it is an immune disease. The schistosome egg is the primary parasite factor responsible for the overt disease. The eggs release the soluble antigen, which induces intensive tissue reaction, a granulomatous reaction to the eggs. If granuloma formation could be suppressed, overt disease might not develop. Praziquantel is an effective antischistosomal drug especially for adult worms. However, whether praziquantel has a suppressing effect on granuloma formation around schistosome eggs directly remains unclear. The purpose of the present study was to investigate the effect of praziquantel, especially administered persistently, on granuloma formation around Schistosoma japonicum eggs in the lung of sensitized mice. Thirty-six mice were divided into three groups averagely. Group A was a control group. First, the mice were injected with schistosomal eggs hypodermically in abdomen, and 10 days later injected with schistosomal eggs intravenously via a tail vein. Group B was a praziquantel short administration group. In addition to the injections of schistosomal eggs as the same of Group A, the mice were administered with praziquantel in a daily dose of 300 mg/kg for 3 days, from 1 day before the intravenous injection of the eggs. Group C was a praziquantel prolonged administration group. In addition to the injections of schistosomal eggs as the same of Group A, the mice were administered with praziquantel in a daily dose of 150 mg/kg for 5 days weekly until the mice were sacrificed. Three mice of each group were sacrificed on days 7, 14, 28, and 56, respectively after the intravenous injection of the eggs, and the lung tissues were fixed with formalin and the slices were HE stained. The granulomas containing eggs in their centers were selected, and 25-30 granulomas from the animals of each group were measured at each time period. The mean areas of egg granulomas of each group were calculated, and the neutrophilic granulocytes, eosinocytes, lymphocytes, fibroblasts, and macrophages within the egg granulomas were counted. The mean numbers of them of each group were calculated. All the data of each group were analyzed and compared statistically. On day 56 after the intravenous injection of the eggs, the mean area of schistosomal egg granulomas in group B was (227.4 ± 728.0) × 10(3) µm(2), less than that of [(297.9 ± 153.3) × 10(3) µm(2)] in group A, and the suppression rate was 23.7% (P < 0.05). On days 7, 14, 28, and 56, the mean areas of schistosomal egg granulomas in group C were (575.8 ± 155.6) × 10(3) µm(2), (310.5 ± 854.0) × 10(3) µm(2), (267.7 ± 513.3) × 10(3) µm(2), and (214.9 ± 446.4) × 10(3) µm(2), respectively, significantly less than those of [(692.7 ± 232.6) × 10(3) µm(2), (439.4 ± 165.0) × 10(3) µm(2), (385.7 ± 129.3) × 10(3) µm(2), and (297.9 ± 153.3) × 10(3) µm(2)] in group A. The suppression rates were 16.9%, 29.3%, 30.6%, and 27.9%, respectively (P values <0.05). On day 56, the mean numbers of neutrophilic granulocytes were 11.4 ± 5.0 in group A and 5.2 ± 3.1 in group C, respectively, with the suppression rate of 54.4% in group C (P < 0.05). On day 56, the mean numbers of eosinocytes within the egg granulomas were 2.3 ± 2.0, 0.1 ± 0.3, and 0.3 ± 0.6 in groups A, B, and C, respectively, with the suppression rate of 95.7% in group B and 87.0% in group C (P values <0.05). On day 56, the mean numbers of macrophages within egg granulomas were 14.3 ± 6.9 in group C, compared with 18.6 ± 8.2 in group A, the suppression rate was 23.1% (P < 0.05). On day 56, the mean numbers of fibroblasts within the egg granulomas were 6.6 ± 4.4 and 5.8 ± 2.6 in groups B and C, respectively, and compared with 14.3 ± 7.8 in group A, the increasing extents decreased by 53.8% and 59.4%, respectively (P values <0.05). Therefore, the administration of praziquantel, especially the prolonged administration, can suppress the formation of schistosomal egg granulomas, including reduction in the areas of granulomas and suppression of the inflammatory cells and the hyperplasia of fibroblasts within granulomas.